Renal transplantation(Tx) is the treatment of choice for patients with ESRD. Transplanted kidneys undergo numerous insults including cold ischemia & warm reperfusion injury and are also subject to nephrotoxicity due to calcineurin inhibitors. These stresses can alter the expression and functional capacity of renal drug transporters. The objective of this study is to evaluate the function of OAT1/3 & MRP2/4 transporters in renal-Tx recipients.

This is a prospective single center study to evaluate changes in renal allograft secretory function following Tx. Cefoxitin, a drug cleared by OAT1/3 & MRP2/4 mediated tubular secretion was used as a renal secretion marker. Living & deceased donor de novo renal transplant recipients(LDRT: n=8; DDRT: n=7) on tacrolimus treatment were consented and cefoxitin pharmacokinetics(PK) was evaluated at <2 wks post-Tx & at ≥3 mo post-Tx. A single dose of 200mg cefoxitin was administered as an IV push and 4ml blood was collected over 4 hr following administration. Cefoxitin concentration in plasma was measured using a validated UPLC/MS/MS method. Historical controls of cefoxitin in the presences and absence of probenecid(OAT/MRP inhibitor) was used to compare results.

Cefoxitin renal clearance, renal secretory clearance and half-life was significantly lower in renal-Tx recipients when compared to healthy controls. There was no statistical difference in cefoxitin PK parameters between renal-Tx recipients and healthy controls that received probenecid prior to cefoxitin administration.

The study suggests that organic anionic transport capacity of renal transplant recipients on tacrolimus and other medications is compromised despite normal filtration function. Reduced activity of organic anionic transporters is expected to increase the systemic exposure of anionic drugs that are primarily renally secreted in renal-Tx patients.

CITATION INFORMATION: Kalluri H, Sood P, Randhawa P, Hariharan S, Tevar A, Humar A, Venkataramanan R. Renal Secretion of Organic Anionic Drugs Is Compromised in Renal Transplant Patients. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress